The collagen network plays a critical role in determining functional properties of cartilage and other extracellular matrices. The collagen network exerts a retractive stress on the osmotically active proteoglycans that are trapped within it in much the same way a balloon's rubber membrane exerts a hydrostatic pressure on the gas contained within it. Until recently, however, it has not been possible to measure important physical/chemical properties of the collagen network independently of the other constituents within the extracellular matrix. However, we devised a new methodology to determine structural properties of the collagen network per se, such as its bulk modulus. This new approach entails modeling the cartilage tissue matrix as a composite material consisting of two distinct phases: a collagen network and a proteoglycan (PG) solution trapped within it; applying various known levels of equilibrium osmotic stress; and using physical-chemical principles and additional experiments to determine a "pressure-volume" relationship for both the PG and collagen phases independently. In pilot studies, we used this approach to determine pressure-volume curves for the collagen network and the PG phases in native and in trypsin treated normal human cartilage specimen, as well as in cartilage specimen from osteoarthritic (OA) joints. In both normal and trypsin-treated specimen, collagen network stiffness appeared unchanged,whereas in the OA specimen, collagen network stiffness decreased. Our findings highlight the role of the collagen network in limiting normal cartilage hydration, and in ensuring a high PG concentration in the matrix, both of which are essential for effective load bearing in cartilage, but are lost in OA. These data also suggest that the loss of collagen network stiffness, and not the loss or modification of PGs may be the incipient event leading to the subsequent disintegraton of cartilage observed in OA. Previously, Kimberlee Potter initiated microscopic Magnetic Resonance Imaging (MRI) studies designed to estimate parameters of our mathematical model of cartilage swelling noninvasively by attempting to relate the chemical composition of cartilage tissue grown in a hollow-fiber bioreactor to various measurable MRI quantities. Ferenc Horkay is now developing an instrument that will enable us to study swelling properties of extremely thin cartilage sections, permitting us to obtain a profile its functional properties with depth from a joint's articular surface.